Abstract Individuals with Down syndrome (DS) are at elevated risk for Attention Deficit and Hyperactivity Disorder (ADHD). This comorbidity is associated with adaptation difficulties among individuals with DS throughout their lifespan, and contributes to the pronounced financial burden associated with health care for individuals with DS and their families. Comorbid ADHD, therefore, is a major health concern for individuals with DS. However, there is currently no scientific foundation for the early detection and treatment of this comorbidity. To address this gap in our knowledge, this project will adopt an innovative retrospective research design that will allow us to leverage a wealth of existing data on a large cohort of infants with DS (n= 78), and then link those data to the current presentation of ADHD symptoms and cognition at 4-5 years. We will also examine the role of biomedical risk in the link between infant cognition and later ADHD symptoms, with an examination of the moderating effects of sleep disturbance, congenital heart defects, prematurity, and other conditions that occur frequently in DS. We will use an advanced quantitative analytic approach utilizing latent variable models within a structural equation modeling framework to examine these longitudinal associations. Findings from this study will facilitate earlier detection of comorbid psychiatric symptoms and directly address the DS INCLUDE objective of ?defining the presentation and course of co-occurring conditions in individuals with DS? to inform future treatment innovations and improve adaptation in this population.